E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007864 |
E.1.2 | Term | Celiac disease |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary efficacy endpoint of this study is change in intestinal mucosal morphology as determined by changes in villus height to crypt depth ratio from baseline to post treatment.
Primary safety endpoints: * Safety and tolerability of ALV003 * Pharmacokinetics of ALV003 * Antibody response to ALV003 |
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E.2.2 | Secondary objectives of the trial |
Secondary efficacy endpoints include change from baseline to post treatment of: * Change in small bowel mucosal inflammation * Density of intraepithelial lymphocutes * IgA deposist on TG2 * Change in serologic markers of celiac disease * IgA class TG2 antibodies * IgA and IgG class deamidated gliadin peptide antibodies * Serum IgA class endomysial antibodies |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age 18 to 75
History of biopsy-proven celiac disease (hospital records or the Social Insurance Institution of Finland, KELA, issued certificate)
Adherence to a gluten-free diet for at least 12 months prior to randomization (documented by medical history)
TG2 antibody negative tested using the rapid point-of-care finger tip whole blood test (Biocard TM Celiac Test, AniBiotech Ltd., Vantaa, Finland)
No history of acute illness for the past 4 weeks
Willing to consume a large meal (e.g. dinner) each day, adhere to a 6-week gluten challenge and undergo 2 on-study upper gastrointestinal endoscopies including multiple biopsies
Signed informed consent |
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E.4 | Principal exclusion criteria |
Active dermatitis herpetiformis lesions at the time of screening
History of IgE-mediated reactions to gluten
Any clinical contraindication to performing an endoscopy with intestinal biopsy
Received any systemic biologics within 6 months prior to study start
Taking any oral probiotic supplements (not including probiotics contained in commercially available food preparations)
Use of any immunosuppressive medications 6 months prior to study start
Use of systemic cortisone-like medications within 28-days prior to and during study treatment
History of alcohol abuse or illicit drug use (e.g. amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, etc.) within past 12 months
Laboratory values: Elevated liver function tests (ALT, AST, Alk Phos and GGT > 2.5 times the upper limit of normal (ULN) Bilirubin > 1.5 ULN Serum creatinine > 1.5 ULN Hemoglobin < 10 g/dL or 100 g/L Calcium < 2.0 mmol/L Platelet count < 75.0 x 109 /L or 75,000/mm3 Partial thromboplastin time (PTT) or prothrombin time (PT/INR) > 1.5 ULN Serum potassium < 3.0 mmol/L, > 5 mmol/L Total white blood cell count (WBC) < 3.0 x 109/L or 3000/mm3 Total lymphocyte < 1.0 x 109/L or 1000/mm3
Current untreated or active peptic ulcer disease, Grade B or greater esophagitis, motility disorders such as irritable bowel syndrome, functional dyspepsia, inflammatory bowel disease, and symptomatic GERD (gastroesophageal reflux disease) other than celiac disease
Positive pregnancy test at screening and just prior to gluten challenge
Unwilling to practice highly effective birth control (unless surgically sterilized or post-menopausal)
Other than oral contraceptives, use of prescribed meds or over-the-counter medications that in the opinion of the Principal Investigator (PI) might interfere with study results
Current use of anticoagulants, including but not limited to, warfarin sodium, heparin, full-dose aspirin or clopidogrel, during the 7-day period prior to randomization
Received any experimental drug within 14 days of randomization; in the case of experimental biologics at least 6 months prior to randomization
The existence of any uncontrolled chronic disease or condition [for example HIV-AIDS, hepatitis, Type 1 or 2 diabetes, or cancer (other than skin cancer)], other than celiac disease
Uncontrolled complications of celiac disease, which in the opinion of the PI could affect immune response, or pose an increased risk to the patient (e.g. type 1 diabetes or other autoimmune disease)
Known allergy or hypersensitivity to any of the components of the placebo, ALV003, E.coli, or E. coli-derived proteins
Known adverse respiratory effects caused by sulfites
Any medical condition, other than celiac disease, which, in the opinion of the study PI could adversely affect the patient’s participation in the trial
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: Intestinal mucosal morphology * Change from baseline to post-treatment in villus height to crypt depth ratio
Primary Safety End Points: * Safety and tolerability of ALV003 * Pharmacokinetics of ALV003 * Antibody response to ALV003
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |